News : 2019 : October

Environmental Influences in PD

Researchers investigate DNA Methylation in regions of the brain affected in Parkinson Disease:

Given the known strong relationship of DNA Methylation with environmental exposure, Dr. Juan Young and Dr. Jeffery Vance at the John P. Hussman Institute for Human Genomics investigated whether brain regions affected in Parkinson disease (PD) were differentially methylated between PD patients and healthy individuals. Their findings were published in the journal Neurology Genetics.

Parkinson disease (PD) is the second most common neurodegenerative disorder affecting older adults. Epigenetics is a potentially important factor contributing to PD risk, particularly since environmental factors have been associated with an increased risk of developing PD. However, relatively little work has been done to explore the potential epigenetic contribution to PD. DNA methylation, the mostly studied form of epigenetic modification, has been primarily investigated in PD within select candidate genes. Drs. Young and Vance, along with Sathesh Sivasankaran, PhD, Lily Wang, PhD, Aleena Ali, Arpit Mehta, David Davis, PhD, Derek Dykxhoorn, PhD, Carol K. Petito, MD, Gary W. Beecham, PhD, Eden R. Martin, PhD, Deborah C. Mash, PhD, Margaret Pericak-Vance, PhD, William K. Scott, PhD, and Thomas J. Montine, MD PhD, performed an initial analysis of the genome-wide methylation profile in the dorsal motor nucleus of the vagus (DMV), substantia nigra (SN), and cingulate gyrus (CG) of PD patients compared with healthy individuals of the same age- and sex match. Each of these brain regions represents the location of neuropathologic changes in PD at different stages of the disease. Their findings indicate that patients with PD have significant DNA methylation changes in these three brain regions, and the largest number of significant DNA methylation changes occur in the DMV. In addition, pathway analysis in the DMV of patients with PD supports the involvement of the Wnt pathway, a critical mediator of cell-to-cell communication and intracellular signaling associated with central nervous system (CNS) development, in the functional changes associated with PD.

This initial study of DNA methylation changes in the DMV, SN, and CG supports the group’s hypothesis of an epigenetic contribution to PD risk. However, it is unknown whether the identified changes are inherited, acquired during early development, in part due to cellular composition changes or induced by environmental variables. This study also supports the increasing data implicating the gastrointestinal tract’s influence on PD through the vagus nerve. It raises the question whether methylation is an early factor in the development of PD, as the DMV is thought to be one of the earliest regions to develop characteristic PD pathologic changes.